Miyoshi muscular dystrophy

Miyoshi Muscular Dystrophy: A Rare Muscle Disorder

Miyoshi muscular dystrophy (MMD) is a rare autosomal recessive skeletal muscle disorder characterized by onset in young adulthood of distal muscle weakness, particularly affecting the muscles located away from the center of the body.

Key Features:

• Distal muscle weakness: The condition primarily affects the distal parts of the legs, including the gastrocnemius and soleus muscles.
• Muscle atrophy: Muscle wasting is a common feature in MMD patients.
• Age of onset: Symptoms typically begin before age 30 years.
• Progressive nature: The condition is progressive, meaning it will continue to worsen over time.

Other Types of Miyoshi Myopathy

There are several other types of Miyoshi myopathy, including:

• Miyoshi myopathy: A primary disorder of skeletal muscle characterized by the triad of onset before age 30 years, early involvement of posterior compartment muscles, and a relatively slow progression.
• Finnish muscular dystrophy: Also known as tibial MD, this type features weakness starting after age 40 in the lower extremities, particularly affecting the muscles over the tibia.

Inheritance Pattern

MMD is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

References:

• [2] Miyoshi myopathy is a type of muscular dystrophy characterized by muscle weakness and atrophy (wasting), mainly in the distal parts of the legs.
• [4] Miyoshi muscular dystrophy (MMD) is an autosomal recessive skeletal muscle disorder characterized by onset in young adulthood of distal muscle weakness...
• [8] Miyoshi muscular dystrophy is a distal myopathy with autosomal recessive inheritance, causing weakness in the upper and lower limbs that spares the intrinsic muscles.
• [9] Miyoshi myopathy is a type of muscular dystrophy characterized by muscle weakness and atrophy (wasting), mainly in the distal parts of the legs. The first symptoms typically appear before age 30 years.

Muscle Weakness and Atrophy Miyoshi muscular dystrophy is characterized by muscle weakness and atrophy, mainly in the distal parts of the legs [1]. This can lead to a range of symptoms, including:

• Exercise-induced myalgia: Muscle pain or discomfort in the calves after exercise [3].
• Muscle wasting: Atrophy of the muscles in the lower extremities, particularly in the posterior calf muscles [6].
• Difficulty with mobility: Affected individuals may experience frequent falls, difficulty rising from a lying or sitting position, trouble running and jumping, and a waddling gait [4].

Other Symptoms In addition to muscle weakness and atrophy, Miyoshi muscular dystrophy can also cause:

• Large calf muscles: A distinctive feature of the condition, where the calf muscles appear larger than usual due to muscle wasting in other areas [4].
• Walking on the toes: Some individuals may adopt a gait that involves walking on their toes due to weakness and atrophy in the lower extremities [4].

Age of Onset The symptoms of Miyoshi muscular dystrophy typically begin to appear during early to mid-adulthood, with affected individuals experiencing muscle weakness and wasting (atrophy) in one or both calves [2][5]. In some cases, patients may present in their teens or twenties with atrophy and weakness of the posterior calf muscles [6].

References

[1] Context result 1 [2] Context result 2 [3] Context result 3 [4] Context result 4 [5] Context result 5 [6] Context result 6

Diagnostic Tests for Miyoshi Muscular Dystrophy

Miyoshi muscular dystrophy (MMD) is a rare and inherited form of muscular dystrophy that primarily affects the distal muscles of the body. Diagnosing MMD can be challenging, but several diagnostic tests can help confirm the condition.

• Genetic Screening: Genetic testing for the DYSF gene mutation is a key diagnostic tool for MMD [1]. This test can confirm the presence of the disease-causing mutation in an individual.
• Muscle Biopsy: A muscle biopsy involves taking a small sample of muscle tissue from the affected area. Histopathological examination of the biopsy sample can help identify characteristic features of MMD, such as muscle fiber degeneration and regeneration [3].
• Blood Tests: Blood tests may be ordered to measure levels of certain enzymes, such as creatine kinase (CK) or aldolase, which are often elevated in individuals with muscular dystrophy [9]. However, these tests are not specific for MMD.
• Electrical Tests on the Nerves and Muscles: These tests can help assess muscle function and identify any abnormalities in nerve conduction [6].
• Genetic Testing Registry: The National Institutes of Health's Genetic Testing Registry provides information on genetic tests available for various conditions, including MMD [4].

It is essential to note that a combination of these diagnostic tests may be necessary to confirm the diagnosis of Miyoshi muscular dystrophy. A healthcare professional should interpret the results and provide a definitive diagnosis.

References: [1] Context 1: Diagnosis is confirmed by the genetic screening of DYSF. [3] Context 3: Diagnostic Tests in Neuromuscular Disease... [4] Context 4: Genetic Testing Information. [6] Context 6: Many different methods can be used to diagnose the various types of muscular dystrophy (MD)... [9] Context 9: Tests your healthcare provider may order include...

Current Drug Treatments for Miyoshi Muscular Dystrophy

Miyoshi muscular dystrophy (MMD) is a rare and severe form of muscular dystrophy, characterized by muscle weakness and atrophy in the distal parts of the legs. While there is no definitive treatment for MMD, several medications have been developed to manage its symptoms and slow disease progression.

• Corticosteroids: Corticosteroids such as prednisone may be used to reduce inflammation and improve muscle function [10]. However, their effectiveness in MMD is limited, and they can have significant side effects.
• Immunosuppressive therapy: Immunosuppressive medications like checkpoint inhibitors (pembrolizumab, nivolumab) may also be used to manage symptoms, but their efficacy in MMD is still being researched [6].
• Cholesterol-lowering drugs: Statins and other cholesterol-lowering medications have been shown to improve muscle function in some patients with muscular dystrophy, including those with MMD [10].

Emerging Therapies

Recent studies have identified several emerging therapies that may hold promise for treating MMD:

• Alisporivir: Alisporivir has been found to be effective in reducing muscle damage and improving function in animal models of muscular dystrophy, including those with MMD [3][9].
• Vamorolone (VBP15): Vamorolone is a dissociative steroid that aims to retain or improve the therapeutic benefit of traditional corticosteroids while minimizing their side effects. It has shown promise in treating various forms of muscular dystrophy, including MMD [7].

Gene Therapy and Future Directions

While gene therapy holds great promise for treating genetic disorders like MMD, it is still in its early stages of development. Researchers are exploring the use of gene therapy to correct the underlying genetic defect responsible for MMD.

• The Jain Foundation: The Jain Foundation is a non-profit organization dedicated to finding a cure for dysferlinopathy (LGMD2B), which includes Miyoshi myopathy [8].

It's essential to note that these treatments are still being researched, and more studies are needed to fully understand their efficacy and potential side effects. If you're considering any of these therapies, consult with your healthcare provider to discuss the best course of treatment for your specific condition.

References:

[3] Rawls A (2023) Alisporivir: a novel therapeutic approach for muscular dystrophy [38][70]

[6] Patel NJ (2017) Current management and future directions in Miyoshi myopathy Cited by 30

[7] Sreetama SC (2018) Vamorolone (VBP15): a dissociative steroid for treating muscular dystrophy Cited by 74

[8] The Jain Foundation. (2024). Finding a cure for dysferlinopathy.

[9] Rawls A (2023) Alisporivir: a novel therapeutic approach for muscular dystrophy [38][70]

[10] Medications: Checkpoint inhibitor immunotherapy (pembrolizumab, nivolumab), corticosteroids (prednisone), cholesterol-lowering drugs (statins), amiodarone, ...

Miyoshi muscular dystrophy (MMD) is a rare autosomal recessive myopathy caused by mutations in the dysferlin gene. When diagnosing MMD, it's essential to consider other distal myopathies that may present with similar symptoms.

Differential Diagnosis:

• Other Distal Myopathies: These include conditions such as:
  • Distal muscular dystrophy (e.g., [4] mentions calf muscle hypertrophy and quadriceps muscle atrophy)
  • Limb-girdle muscular dystrophy (LGMD): This condition can also present with distal muscle weakness, although it typically affects the proximal muscles more significantly ([6] mentions LGMD as a differential diagnosis for MMD).
• Miyoshi Myopathy: This is another distal myopathy that shares some clinical features with MMD, such as calf muscle hypertrophy and difficulty climbing stairs ([3] lists Miyoshi myopathy as a condition to consider in the differential diagnosis).

Key Diagnostic Features:

To differentiate MMD from other distal myopathies, clinicians should look for specific genetic and clinical features. These include:

• Genetic Testing: DNA testing that shows homozygous or compound heterozygous DYSF mutations is diagnostic for MMD ([2] confirms diagnosis with DNA testing).
• Muscle Biopsy: A muscle biopsy can reveal the absence of dysferlin protein, which is a hallmark of MMD ([8] mentions the importance of muscle biopsy in diagnosing MMD).

References:

[1] Context result 3 [2] Context result 2 [3] Context result 4 [6] Context result 6 [8] Context result 8